Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (...Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% - 10%) exhibit two distinct cell size subpopulations, in the 2.5 μM - 5.0 μM and 5.0 μM - 8.0 μM range. In addition to IgA, about 60% of the cells expressed a novel heterodimeric IgA/IgG immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, IgA, IgG, CD45, and COX-2. We assume that they originated from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.展开更多
Gastric cancer(GC) is one of the leading causes of cancerrelated mortality worldwide.Cancer stem cells(CSCs),which were first identified in acute myeloid leukemia and subsequently in a large array of solid tumors,play...Gastric cancer(GC) is one of the leading causes of cancerrelated mortality worldwide.Cancer stem cells(CSCs),which were first identified in acute myeloid leukemia and subsequently in a large array of solid tumors,play important roles in cancer initiation,dissemination and recurrence.CSCs are often transformed tissue-specific stem cells or de-differentiated transit amplifying progenitor cells.Several populations of multipotent gastric stem cells(GSCs) that reside in the stomach have been determined to regulate physiological tissue renewal and injury repair.These populations include the Villin+ and Lgr5+ GSCs in the antrum,the Troy+ chief cells in the corpus,and the Sox2+ GSCs that are found in both the antrum and the corpus.The disruption of tumor suppressors in Villin+ or Lgr5+ GSCs leads to GC in mouse models.In addition to residing GSCs,bone marrow-derived cells can initiate GC in a mouse model of chronic Helicobacter infection.Furthermore,expression of the cell surface markers CD133 or CD44 defines gastric CSCs in mouse models and in human primary GC tissues and cell lines.Targeted elimination of CSCs effectively reduces tumor size and grade in mouse models.In summary,the recent identification of normal GSCs and gastric CSCs has greatly improved our understanding of the molecular and cellular etiology of GC and will aid in the development of effective therapies to treat patients.展开更多
Objective： To study the effects of Weipixiao （胃痞消, WPX） on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions （GPL）. Methods： Sprague Dawley rats w...Objective： To study the effects of Weipixiao （胃痞消, WPX） on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions （GPL）. Methods： Sprague Dawley rats were randomly divided into control, model, vitacoenzyme （0.2 g·kg-l·day-1）, WPX high-dose （H-WPX, 15 g·kg-l·day-1）, WPX medium-dose （M-WPX, 7.5 g·kg-1·day-1） and WPX low-dose （L-WPX, 3.75 g·kg-l·day-1） groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-protein- coupled receptor 5 （Lgr5）, matrix metalloproteinase-7 （MMP-7）, Wntl, Wnt3a, and 13 -catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software. Results： Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wntl, Wnt3a and 13 -catenin than those of the control group （P〈0.01）. Interestingly, we also observed Lgr5＋ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wntl, and 13-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups （P〈0.05）. A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups （P〉0.05）. Conclusion： Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wntl, β -catenin and the aberrant activation of Wnt/β -catenin pathway.展开更多
目的探讨含亮氨酸重复序列G-蛋白偶联受体5(1eucine-rich repeat-containing G protein coupled receptor 5,Lgr5)及CD44在卵巢癌中的表达及其与预后的关系。方法选取2006年5月至2010年1月住院并接受手术治疗的卵巢癌患者140例,选取同...目的探讨含亮氨酸重复序列G-蛋白偶联受体5(1eucine-rich repeat-containing G protein coupled receptor 5,Lgr5)及CD44在卵巢癌中的表达及其与预后的关系。方法选取2006年5月至2010年1月住院并接受手术治疗的卵巢癌患者140例,选取同期本院因卵巢良性病变行肿物剥除或附件切除的40例患者作为对照,应用免疫组化(S-P)方法检测140例卵巢癌组织(卵巢癌组)、140例卵巢癌癌旁组织(癌旁组)、正常卵巢组织40例(正常组)中的Lgr5及CD44蛋白表达,分析其与卵巢癌患者临床病理指标的关系。结果 (1)Lgr5在正常卵巢组织、癌旁组织和卵巢癌中的阳性率分别为5.0%、18.3%和95.7%,差异具有统计学意义(F=24.581,P=0.001);CD44在正常卵巢组织、癌旁组织和卵巢癌中的阳性率分别为7.5%、15.7%和90.0%,差异具有统计学意义(P<0.05)。(2)Lgr5表达与肿瘤分化程度、淋巴结转移及TNM分期有关(P<0.05)。CD44表达与肿瘤分化程度、浸润深度、淋巴结转移及TNM分期有关(P<0.05)。(3)Lgr5及CD44存在正相关性(r=0.3,P<0.05)。(4)Lgr5高表达者(+++)和低表达者(+)^(++)5年总生存率分别为29.2%和51.2%(HR=11.637,95%CI:4.351~18.439;P=0.002);CD44高表达者(+++)和低表达者(+)^(++)5年总生存率分别为35.3%和41.3%(HR=10.142,95%CI:4.285~17.013;P=0.006)。结论 Lgr5及CD44的增强表达与卵巢癌侵袭性增强有密切关系,其表达可作为判断卵巢癌患者预后的指标。展开更多
Pancreatic cancer(PC) has been one of the deadliest of all cancers, with almost uniform lethality despite aggressive treatment. Recently, there have been important advances in the molecular, pathological and biologica...Pancreatic cancer(PC) has been one of the deadliest of all cancers, with almost uniform lethality despite aggressive treatment. Recently, there have been important advances in the molecular, pathological and biological understandingof pancreatic cancer. Even after the emergence of recent new targeted agents and the use of multiple therapeutic combinations, no treatment option is viable in patients with advanced cancer. Developing novel strategies to target progression of PC is of intense interest. A small population of pancreatic cancer stem cells(CSCs) has been found to be resistant to chemotherapy and radiation therapy. CSCs are believed to be responsible for tumor initiation, progression and metastasis. The CSC research has recently achieved much progress in a variety of solid tumors, including pancreatic cancer to some extent. This leads to focus on understanding the role of pancreatic CSCs. The focus on CSCs may offer new targets for prevention and treatment of this deadly cancer. We review the most salient developments in important areas of pancreatic CSCs. Here, we provide a review of current updates and new insights on the role of CSCs in pancreatic tumor progression with special emphasis on Dcl K1 and Lgr5, signaling pathways altered by CSCs, and the role of CSCs in prevention and treatment of PC.展开更多
文摘Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% - 10%) exhibit two distinct cell size subpopulations, in the 2.5 μM - 5.0 μM and 5.0 μM - 8.0 μM range. In addition to IgA, about 60% of the cells expressed a novel heterodimeric IgA/IgG immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, IgA, IgG, CD45, and COX-2. We assume that they originated from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.
基金Supported by Fundamental Research Funds for the Central Universities lzujbky-2013-221China’s National Science and Technology Program for Public Wellbeing Grant No.2012GS620101Major Science and Technology Projects of Gansu Province Grant No.1102FKDA006
文摘Gastric cancer(GC) is one of the leading causes of cancerrelated mortality worldwide.Cancer stem cells(CSCs),which were first identified in acute myeloid leukemia and subsequently in a large array of solid tumors,play important roles in cancer initiation,dissemination and recurrence.CSCs are often transformed tissue-specific stem cells or de-differentiated transit amplifying progenitor cells.Several populations of multipotent gastric stem cells(GSCs) that reside in the stomach have been determined to regulate physiological tissue renewal and injury repair.These populations include the Villin+ and Lgr5+ GSCs in the antrum,the Troy+ chief cells in the corpus,and the Sox2+ GSCs that are found in both the antrum and the corpus.The disruption of tumor suppressors in Villin+ or Lgr5+ GSCs leads to GC in mouse models.In addition to residing GSCs,bone marrow-derived cells can initiate GC in a mouse model of chronic Helicobacter infection.Furthermore,expression of the cell surface markers CD133 or CD44 defines gastric CSCs in mouse models and in human primary GC tissues and cell lines.Targeted elimination of CSCs effectively reduces tumor size and grade in mouse models.In summary,the recent identification of normal GSCs and gastric CSCs has greatly improved our understanding of the molecular and cellular etiology of GC and will aid in the development of effective therapies to treat patients.
基金Supported by the National Natural Science Foundation of China(No.81273739)
文摘Objective： To study the effects of Weipixiao （胃痞消, WPX） on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions （GPL）. Methods： Sprague Dawley rats were randomly divided into control, model, vitacoenzyme （0.2 g·kg-l·day-1）, WPX high-dose （H-WPX, 15 g·kg-l·day-1）, WPX medium-dose （M-WPX, 7.5 g·kg-1·day-1） and WPX low-dose （L-WPX, 3.75 g·kg-l·day-1） groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-protein- coupled receptor 5 （Lgr5）, matrix metalloproteinase-7 （MMP-7）, Wntl, Wnt3a, and 13 -catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software. Results： Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wntl, Wnt3a and 13 -catenin than those of the control group （P〈0.01）. Interestingly, we also observed Lgr5＋ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wntl, and 13-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups （P〈0.05）. A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups （P〉0.05）. Conclusion： Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wntl, β -catenin and the aberrant activation of Wnt/β -catenin pathway.
文摘目的探讨含亮氨酸重复序列G-蛋白偶联受体5(1eucine-rich repeat-containing G protein coupled receptor 5,Lgr5)及CD44在卵巢癌中的表达及其与预后的关系。方法选取2006年5月至2010年1月住院并接受手术治疗的卵巢癌患者140例,选取同期本院因卵巢良性病变行肿物剥除或附件切除的40例患者作为对照,应用免疫组化(S-P)方法检测140例卵巢癌组织(卵巢癌组)、140例卵巢癌癌旁组织(癌旁组)、正常卵巢组织40例(正常组)中的Lgr5及CD44蛋白表达,分析其与卵巢癌患者临床病理指标的关系。结果 (1)Lgr5在正常卵巢组织、癌旁组织和卵巢癌中的阳性率分别为5.0%、18.3%和95.7%,差异具有统计学意义(F=24.581,P=0.001);CD44在正常卵巢组织、癌旁组织和卵巢癌中的阳性率分别为7.5%、15.7%和90.0%,差异具有统计学意义(P<0.05)。(2)Lgr5表达与肿瘤分化程度、淋巴结转移及TNM分期有关(P<0.05)。CD44表达与肿瘤分化程度、浸润深度、淋巴结转移及TNM分期有关(P<0.05)。(3)Lgr5及CD44存在正相关性(r=0.3,P<0.05)。(4)Lgr5高表达者(+++)和低表达者(+)^(++)5年总生存率分别为29.2%和51.2%(HR=11.637,95%CI:4.351~18.439;P=0.002);CD44高表达者(+++)和低表达者(+)^(++)5年总生存率分别为35.3%和41.3%(HR=10.142,95%CI:4.285~17.013;P=0.006)。结论 Lgr5及CD44的增强表达与卵巢癌侵袭性增强有密切关系,其表达可作为判断卵巢癌患者预后的指标。
基金In part by Kerley Cade Endowed Chair(Chinthalapally V Rao),University of Oklahoma Health Sciences Centerin part support from the National Cancer Institute,No.5R03CA181584-02(Altaf Mohammed)
文摘Pancreatic cancer(PC) has been one of the deadliest of all cancers, with almost uniform lethality despite aggressive treatment. Recently, there have been important advances in the molecular, pathological and biological understandingof pancreatic cancer. Even after the emergence of recent new targeted agents and the use of multiple therapeutic combinations, no treatment option is viable in patients with advanced cancer. Developing novel strategies to target progression of PC is of intense interest. A small population of pancreatic cancer stem cells(CSCs) has been found to be resistant to chemotherapy and radiation therapy. CSCs are believed to be responsible for tumor initiation, progression and metastasis. The CSC research has recently achieved much progress in a variety of solid tumors, including pancreatic cancer to some extent. This leads to focus on understanding the role of pancreatic CSCs. The focus on CSCs may offer new targets for prevention and treatment of this deadly cancer. We review the most salient developments in important areas of pancreatic CSCs. Here, we provide a review of current updates and new insights on the role of CSCs in pancreatic tumor progression with special emphasis on Dcl K1 and Lgr5, signaling pathways altered by CSCs, and the role of CSCs in prevention and treatment of PC.
